Bated Breath

Many of the medical interventions put in place to ensure the survival of a premature baby need to be balanced against a large number of serious side-effects.

By Rebecca Lim

Medical advances are enabling increasingly premature babies to survive, but the health risks they face can persist well beyond childhood. Now a clinical trial in Melbourne is testing the use of foetal stem cells to ward off chronic lung disease in premature babies.

Babies born prematurely have a pretty rough start to life. Not surprisingly, this becomes more problematic for extremely premature babies born within the first 26 weeks of pregnancy.

This is a bit of a catch-22, since improvements in obstetric and neonatal care are leading to increasing number of deliveries of extremely premature babies.

In fact, these days babies as premature as 22 weeks of gestation are now born alive, albeit with health problems.

A mere two decades ago, these babies would have been considered non-viable births. As a result, obstetric care and neonatal management dance a tight tango to rapidly develop clinical management protocols that keep these babies alive with as few developmental problems as possible.

The more premature a baby is, the more developmental milestones need to be achieved postnatally. One of these major milestones is lung development. The lungs of a premature baby do not have the complex alveolar structures needed for essential gas exchange.

Steroids such as dexamethasone or hydrocortisone are given to mothers prior to preterm labour. These help speed up the development of the lungs to reduce the incidence of respiratory distress syndrome and related complications following premature birth.

Steroids are also given to premature babies after birth to improve lung function and stabilise low blood pressure, both of which are common problems in severely premature babies. However, a vast number of extremely premature babies will also require ventilation, and these babies are at increased risk of a chronic lung disease called bronchopulmonary dysplasia.

Many of the medical interventions put in place to ensure the survival of a premature baby need to be balanced against a large number of serious side-effects. For instance, the steroids given to aid lung development slow down the growth of the developing brain, and there have been reports of increased incidence of cerebral palsy and neurodevelopmental handicap in babies given steroids. The risks and benefits of many of these medical interventions have to be carefully balanced because the clinical stability of extremely premature babies can be precarious.

There is currently no cure for bronchopulmonary dysplasia, and once it develops the survivors of moderate to severe disease continue to be at risk of developing serious lung complications in adolescence and adulthood. Often this is in the shape of misdiagnosed asthma or emphysema, but it is now clear that the early maldevelopment resulting from bronchopulmonary dysplasia is most likely the cause.

There is thus an urgent need to find a safe and efficacious cure for diseases such as bronchopulmonary dysplasia. A recent candidate is cell-based therapy.

The subject of stem cells and regenerative medicine is broad and encompasses a vast number of diseases across the entire lifespan – virtually from cradle to grave. Academic research teams and the cell banking industry are working in a concerted effort to identify stem cell sources, types and therapeutic applications for stem cells isolated from the afterbirth.

Umbilical cord blood, Wharton’s jelly, placenta and foetal membranes are rich in stem cells and stem-like cells. All of these tissues are considered biological waste and are usually discarded after a baby is born. A major advantage of using cells from these tissues is the avoidance of ethical concerns associated with more traditional stem cells such as embryonic stem cells.

Stem cells of foetal origin have greater regenerative potential than adult tissue sources such as adipose tissue and bone marrow. Furthermore, if cells are to be isolated from the baby’s own afterbirth, there would be no need to find a suitable donor. Given the critical condition of premature babies, expediency of treatment could make a significant difference to the final outcome.

Of the variety of stem cells isolated from the afterbirth, cord blood stem cells are currently the most commonly used, although they are predominantly used for haematological diseases. There are public and private cord blood banks worldwide. In Australia, 11 hospitals are part of the National Cord Blood Collection and Banking Network, AusCord, where the donation of cord blood is a voluntary and personal choice. A growing number of private cord blood banks provide expectant parents with a kit enabling the collection of stem cells at the time of birth.

There are, however, a number of considerations with stem cell banking for perinatal use. The volume of cord blood that can be collected from an extremely premature baby will be much lower compared with a healthy term baby. Also, there is insufficient evidence to indicate that stem cells from premature babies will be equally effective. This line of argument also applies to other stem cell types. There may therefore be a need to use stem cells from healthy term babies.

Regardless, cell therapies hold great promise for diseases affecting premature babies. Epithelial cells from the amniotic membranes are well-tolerated by the recipient’s immune system without any evidence of tissue rejection. They have potent regenerative properties and can be isolated in numbers sufficient for therapeutic use without the need for culture expansion.

Animal model studies indicate that amniotic epithelial cells can help lung repair in cases of bronchopulmonary dysplasia by switching the immune system to an anti-inflammatory state while triggering repair processes in the lungs.

With these very promising results, a Phase I clinical trial is due to take place at Monash Medical Centre in Melbourne. A team of clinicians and scientists are working to translate research findings to a curative therapy for bronchopulmonary dysplasia in premature babies.

While we are still in the very early years of developing cell-based therapies for extremely premature babies, it is with bated breath that we hope to find cures for these most vulnerable of patients.

Rebecca Lim is a Research Fellow in the Faculty of Medicine, Nursing and Health Sciences at Monash University. This article was first published in Issues (www.issuesmagazine.com.au).

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